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Optimising breast magnetic resonance imaging

Federica Pediconi and Marianna Telesca
9 June, 2014  
Hospital Healthcare Europe spoke with Federica Pediconi and Marianna Telesca about the optimisation of magnetic resonance imaging in breast disease
 
Federica Pediconi MD
Marianna Telesca MD
Department of Radiological Sciences,
University of Rome “La Sapienza”, Italy
 
We first introduced contrast-enhanced breast magnetic resonance imaging (MRI) to our facility in 2002. After more than ten years of experience, we would say that breast MR has drastically changed our approach to breast disease as well as patient management. It has increased our diagnostic performance, accelerated patient turnaround and increased our collaboration with the breast team specialists.
 
Basic concepts
MRI of the breast is an important tool for the detection of breast cancer. The use of MRI with contrast agents for the detection of breast cancer was first reported in 1986 by Heywang et al.(1) In a preliminary study, 20 patients underwent breast examinations by MRI, without and with gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) as contrast medium. All carcinomas enhanced, whereas dysplastic tissue enhanced slightly or not at all. Significant additional diagnostic information was available on the Gd-DTPA examinations in at least four of 20 cases compared with MR without contrast medium and X-ray mammography. The preliminary results indicated that MRI of breast using Gd-DTPA might be helpful for the evaluation of dense breasts and the differentiation of dysplasia and scar tissue from carcinoma. 
 
The high sensitivity of MRI for breast cancer has led to the increasing use of MRI for breast cancer detection, assessment, and treatment monitoring, although appropriate indications, scanning technique, and interpretation remain variable among facilities.
 
In our facility we are currently using two magnets with dedicated breast coils: 1.5 Avanto (Siemens) and Discovery MR750 3.0T (GE Healthcare). For scanning, the patient is in the prone position. We first acquire T2w images, with and without fat suppression, followed by dynamic 3D GE T1w images before and after administration of contrast agent.
 
We follow the European Society of Breast Cancer Specialists (EUSOMA) recommendations for indications for breast MRI.(2) The indications are:
  • staging before treatment planning in selected cases (invasive lobular 
  • cancer, high risk lesions, 
  • mammography/ultrasound size
  • discrepancy, partial breast irradiation
  • screening of high-risk women
  • evaluation of response to neoadjuvant chemotherapy
  • patients with breast augmentation 
  • or reconstruction
  • occult primary breast cancer
  • breast cancer recurrence
  • characterisation of equivocal findings at conventional imaging.
 
However, we consider each case separately and carefully evaluate if the patient could benefit from MR, even if the indication is not strictly recognised. 
 
Selection of contrast agent
It has been firmly established that breast MRI should be carried out routinely with Gd-based contrast agent injection, except for the evaluation of breast implant integrity. 
 
According to the literature, we are using what is considered to be the more reliable contrast agent for breast MR in terms of lesion detection, characterisation and patient safety. 
 
We use a high-relaxivity contrast agent for breast MR in our department because studies have proved the better performance of these agents compared with others. There are several advantages of using Gd-based high-relaxivity contrast media in breast MRI. First, they have an increased lesion detection rate. Second, considering that the morphology, the margin delineation and the vascularisation of the breast lesions are crucial for the characterisation, these media lead to a more accurate diagnosis. Last, but not the least, they are safe, with a very low percentage of adverse events.
 
Major studies
Gadobenate dimeglumine versus gadopentetate dimeglumine
In 2005, Pediconi et al prospectively and intra-individually compared equivalent doses of gadobenate dimeglumine and gadopentetate dimeglumine (0.1mmol/kg body weight) for accuracy of detection and characterisation of breast lesions.(3)
 
Twenty-six consecutive women (mean age, 47.8 years) suspected of having a breast tumour at mammography and sonography underwent two identical MR examinations at 1.5T; examinations were separated by more than 48 hours but less than 72 hours. A T1-weighted three-dimensional gradient-echo sequence was used, and images were acquired before and at 0, 2, 4, 6, and 8 minutes after randomised injection of gadopentetate dimeglumine or gadobenate dimeglumine at an identical flow rate of 2ml/sec. Accuracy for lesion detection was determined against a final diagnosis based on findings at conventional mammography, sonography, and surgery. Sensitivity, specificity, positive and negative predictive values, and overall accuracy for malignant lesion identification were determined against histologic results. 
 
MR mammography with gadobenate dimeglumine depicted significantly (p = 0.003) more lesions (45 of 46) than that with gadopentetate dimeglumine (36 of 46), and detected lesions were significantly (p < 0.001) more conspicuous with gadobenate dimeglumine. Comparison of the contrast agents for their ability to help identify malignant lesions revealed significant superiority for gadobenate dimeglumine: sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy for malignant lesion identification were, respectively, 94.7%, 100%, 100%, 80.0%, and 95.6% with gadobenate dimeglumine and 76.3%, 100%, 100%, 47.1%, and 80.4% with gadopentetate dimeglumine. 
 
The study concluded that detection of breast lesions and accurate identification of malignant lesions at MRI are significantly superior with gadobenate dimeglumine compared with gadopentetate dimeglumine.
 
Contralateral breast cancer
Pediconi et al prospectively evaluated the accuracy of gadobenate dimeglumine-enhanced MR mammography for depiction of synchronous contralateral breast cancer in patients with newly diagnosed unilateral breast cancer or high-risk lesions, with histologic analysis or follow-up as reference.(4)
 
A total of 118 consecutive women (mean age, 52 years) with unilateral breast cancer or high-risk lesions and negative findings in the contralateral breast at physical examination, ultrasonography, and conventional mammography underwent gadobenate dimeglumine-enhanced 1.5-T MR mammography. Transverse three-dimensional T1-weighted gradient-echo images were acquired before and at 0, 2, 4, 6, and 8 minutes after gadobenate dimeglumine administration (0.1mmol/kg body weight). Breast Imaging Reporting and Data System (BI-RADS) was used to categorise breast density and the level of suspicion for malignant contralateral breast lesions. Results were compared with histologic findings. Sensitivity, specificity, accuracy, and positive and negative predictive values for contrast-enhanced MR mammography were evaluated.
 
Contrast-enhanced MR mammography revealed contralateral lesions in 28 (24%) of 118 patients. Twenty-four lesions were detected in patients with dense breasts (BI-RADS breast density category III or IV). Lesions in eight (29%) of 28 patients were BI-RADS category 4; patients underwent biopsy. Lesions in 20 (71%) patients were BI-RADS category 5; patients underwent surgery. At histologic analysis, 22 lesions were confirmed as malignant; six lesions were fibroadenomas.
 
No false-negative lesions were detected; none of the fibroadenomas were BI-RADS category 5. The sensitivity, specificity, accuracy, and positive and negative predictive values of contrast-enhanced MR mammography for depiction of malignant or high-risk contralateral lesions were 100%, 94%, 95%, 79%, and 100%, respectively. Follow-up findings (12–24 months) confirmed absence of contralateral lesions in 90 of 118 patients with negative contrast-enhanced MR mammographic findings in the contralateral breast.
 
The authors concluded that contrast-enhanced MR mammography is accurate for detection of synchronous contralateral cancer or high-risk lesions in patients with newly diagnosed breast cancer or high-risk lesions.
 
Superiority of gadobenate dimeglumine
Martincich et al(5) compared 0.1mmol/kg doses of gadobenate dimeglumine and gadopentetate dimeglumine using a prospective, multicentre, double-blind, randomised protocol.
 
A total of 162 women (mean age, 52.8 years) were enrolled at 17 sites in Europe and China between July 2007 and May 2009. Participants underwent at least one breast MRI examination at 1.5T by using three-dimensional spoiled gradient-echo sequences. Of these, 151 women received both contrast agents in randomised order in otherwise identical examinations separated by more than two but less than seven days. Images, acquired at two-minute or shorter intervals after contrast agent injection, were evaluated independently in a blinded fashion. Histopathologic confirmation was available for all malignant lesions (n = 144), while benign lesions were confirmed either by using histopathologic examination (n = 52) or by at least 12-month diagnostic follow-up (n = 20) with mammography and/or ultrasonography. 
 
Readers 1, 2, and 3 noted significant superiority for gadobenate dimeglumine in terms of the malignant lesion detection rate; readers 1, 2, and 3 reported significantly superior diagnostic performance (sensitivity, specificity, and accuracy) for breast cancer detection with gadobenate dimeglumine and significantly superior positive predictive value and negative predictive value (99.0%, 99.4%, 99.4% versus 97.8%, 98.0%, 98.1%, respectively; p ≤ 0.0003). No safety concerns were noted with either agent.
 
The study concluded that gadobenate dimeglumine is superior to gadopentetate dimeglumine for breast cancer diagnosis.
 
Gadobutrol 1.0M versus gadobenate 0.5M
Pediconi et al carried out a study to demonstrate non-inferiority of gadobutrol versus gadobenate dimeglumine by intra-individually comparing 0.1mmol/kg body weight doses for contrast-enhanced breast MRI and prospectively evaluating lesion detection and characterisation in a multicentre trial.(6)
 
Two identical breast MRI examinations were performed in 72 patients with biopsy-proven breast cancer, separated by one to seven days. Gadobutrol 1.0M or gadobenate 0.5M were administered in a randomised order. Lesion detection and characterisation were performed by two independent blinded readers. Lesion tracking, which compared onsite readings and histology from surgery or biopsy, was performed by a third reader. Differences in lesion detection and characterisation were compared between the two contrast agents.
 
Of 103 lesions, 96 were malignant and seven were benign. No difference in lesion detection was identified between the contrast agents (82.33% for gadobutrol; 81.60% for gadobenate). Assessment of sensitivity in lesion characterisation and BI-RADS showed no difference between gadobutrol (92.63%) and gadobenate (90.53%). Regarding morphology, there was more non-focal enhancement for gadobutrol than for gadobenate (p  =  0.0057).
 
Non-inferiority of gadobutrol compared with gadobenate was demonstrated for breast lesion detection and sensitivity in lesion characterisation in breast MRI.
 
Limitations
The use of breast MR in daily clinical practice is increasing and its use is impacting on breast patient management. However, despite the great enthusiasm and the positive results, it is still a costly procedure, not available everywhere, and which requires special training, good breast imaging experience and a dedicated team. Furthermore, it cannot be considered as a separate tool from mammography and ultrasound and needs to be used in a multidisciplinary context.
 
The future
The applications of contrast-enhanced breast MRI have been widely explored; however, there are new interesting aspects to examine. 
 
We think that, beside the conventional breast MRI, the emerging role of the functional imaging needs to be evaluated. For example, techniques such as diffusion weighted imaging and spectroscopy that have a well-recognised role for other organs, should also be applied to the breast. We need to know if they improve the diagnostic performance and, in particular, the specificity of the technique. Furthermore, focusing on the breast disease itself, the impact of breast MR on patient outcome, for example in terms of overall and the disease-free survival rate, should be evaluated. Recently, different studies have evaluated the possibility to perform breast MRI without contrast agent; however, contrast agent will certainly be required in the immediate future.
 
Conclusions
Breast MRI is a technique that is being used increasingly in clinical practice. Technical improvements, such as very high spatial resolution, and innovations such as diffusion-weighted imaging and proton spectroscopy, are expected to enter clinical practice in the near future. Breast cancer specialists should work together to ensure the optimal clinical use of this emerging technology and for future research, focusing on patient outcome as the primary endpoint.
 
References
  1. Heywang SH et al. MR imaging of the breast using gadolinium-DTPA. J Comput Assist Tomogr 1986;10(2):199.
  2. Sardanelli F et al. Magnetic resonance imaging of the breast: Recommendations from the EUSOMA working group. Eur J Cancer 2010;46(8):1296–316.
  3. Pedicono F et al. Breast lesion detection and characterization at contrast-enhanced MR mammography: gadobenate dimeglumine versus gadopentetate dimeglumine. Radiology 2005;237(1):45–56. 
  4. Pediconi F et al. Contrast-enhanced MR mammography for evaluation of the contralateral breast in patients with diagnosed unilateral breast cancer or high-risk lesions. Radiology 2007;243(3):670–80. 
  5. Martincich L et al. Multicenter, double-blind, randomized, intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for breast MR imaging (DETECT Trial). Radiology 2011;258(2):396–408. 
  6. Pediconi F et al. Intra-individual randomised comparison of gadobutrol 1.0 M versus gadobenate dimeglumine 0.5 M in patients scheduled for preoperative breast MRI. Eur Radiol 2013;23(1):84–92; erratum in Eur Radiol 2013;23(8):2100.